Pre-Hospital Diagnosis in Mobile Stroke Unit

ObjectivesMobile stroke unit (MSU) has been shown to rapidly provide pre-hospital thrombolysis in acute ischemic stroke (AIS). MSU encounters neurological disorders other than AIS that require emergent treatment.Methods/MaterialsWe obtained pre-hospital diagnosis and treatment data from the prospectively collected dataset on 221 consecutive MSU encounters. Based on initial clinical evaluation and neuroimaging obtained on MSU, the diagnosis of AIS (definite, probable, and possible AIS, transient ischemic attack), intracranial hemorrhage, and likely stroke mimics was made.ResultsFrom July 2014 to April 2015, 221 patients were treated on MSU. 78 (35%) patients had initial clinical diagnosis of definite/probable AIS or TIA, 69 (31%) were diagnosed as possible AIS or TIA, 15 (7%) had intracranial hemorrhage while 59 patients (27%) were diagnosed as likely stroke mimics. Stroke mimics encountered included 13 (6%) metabolic encephalopathy, 11 (5%) seizures, 9 (4%) migraines, 3 (1%) substance abuse, 2 (1%) CNS tumor, 3 (1%) infectious etiology and 3 (1%) hypoglycemia. Fifty-four (24%) patients received non-thrombolytic treatments on MSUConclusionAbout one third of MSU encounters were not AIS initially, including intracranial hemorrhage and stroke mimics. MSU can be utilized to provide pre-hospital treatments in emergent neurological conditions other than AIS.     

The “oral” history of COVID-19: Primary infection,salivary transmission,and post-acute implications

Severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to more than 3.25 million recorded deaths worldwide as of May 2021. COVID-19 is known to be clinically heterogeneous, and whether the reported oral signs and symptoms in COVID-19 are related to the direct infection of oral tissues has remained unknown. Here, we review and summarize the evidence for the primary infection of the glands, oral mucosae, and saliva by SARS-CoV-2. Not only were the entry factors for SARS-CoV-2 found in all oral tissues, but these were also sites of SARS-CoV-2 infection and replication. Furthermore, saliva from asymptomatic individuals contained free virus and SARS-CoV-2-infected oral epithelial cells, both of which were found to transmit the virus. Collectively, these studies support an active role of the oral cavity in the spread and transmission of SARS-CoV-2 infection. In addition to maintaining the appropriate use of personal protective equipment and regimens to limit microbial spread via aerosol or droplet generation, the dental community will also be involved in co-managing COVID-19 “long haulers”—now termed Post-Acute COVID-19 Syndrome. Consequently, we propose that, as SARS-CoV-2 continues to spread and as new clinical challenges related to COVID-19 are documented, oral symptoms should be included in diagnostic and prognostic classifications as well as plans for multidisciplinary care.     

Disruption of EXOC6B in a patient with developmental delay,epilepsy, and a de novo balanced t(2;8) translocation

Most balanced chromosomal aberrations are not associated with a clinical phenotype, however, in some patients they may disrupt gene structure. With the development of various next-generation sequencing techniques, fast and specific analyses of the breakpoint regions of chromosomal rearrangements are possible. Here, we report on a 19-year-old woman with a de novo balanced translocation t(2;8)(p13.2;q22.1) and a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features. By next-generation sequencing, we defined the breakpoints and found disruption of the exocyst complex component 6B (EXOC6B) gene in intron 1 on chromosome 2p13.2 involving two Alu elements with a homology of 81%. No gene was found at the respective breakpoint on chromosome 8. Expression analysis of the EXOC6B in blood lymphocytes and buccal smear revealed reduced expression in the patient in comparison with the control. Our findings in combination with one recently published case and one other patient listed in DECIPHER v5.1 indicate EXOC6B as a gene relevant for intellectual development and electrophysiological stability.     

Intra-articular pressure profile of the knee joint in a spectrum of inflammatory arthropathies

OBJECTIVES—The intra-articular pressure (IAP) rises significantly after isometric quadriceps contraction in patients with rheumatoid synovitis, a process that may temporarily impede synovial blood flow and cause oxidative injury. In acute traumatic knee effusions (ATE) pressure rises are trivial. This study compared the IAP profiles of patients with ATE with three different populations—an acute synovitis on the background of a chronic inflammatory arthropathy, a chronic low grade inflammatory arthropathy, and an acute intermittent inflammatory arthropathy. The study objective was to discover if the pressure profiles observed in these groups reflect an influence of the inflammatory process or time or both.
METHODS—Thirty three patients were studied. These were divided into four subgroups; group 1: five acute traumatic knee effusions (ATE); group 2: acute effusions on the background of a chronic inflammatory arthropathy: seven rheumatoid arthritis (RA), five psoriatic arthritis (PsA); group 3: seven osteoarthritis (OA) and group 4: acute effusions on the background of an intermittent inflammatory arthropathy: seven pyrophosphate arthropathy (PA), one amyloid (AA), one Behcet's (B). IAP was measured (mm Hg) at rest and during isometric quadriceps contraction using the hand held portable 295-1 intra-compartmental pressure monitor system (Stryker UK). The volume of synovial fluid aspirated was recorded.
RESULTS—Expressed as medians (interquartile range). Resting IAP was; ATE 6 (2-12), RA 8 (5-47), PsA 18 (11-31), OA 17 (7-21), PA 25 (9-29), AA 14, and B 12. IAP increased in all subjects during isometric contraction; ATE 9 (7-16), RA 56 (33-150), PsA 52 (43-85), OA 56 (20-116), PA 53 (41-65), AA 47, B 57 and the IAP rise was significant (p<0.05) in all except the ATE group (p>0.05). The volume of synovial fluid aspirated in groups 2, 3, and 4 correlated significantly with the magnitude of the IAP change (r = 0.45, p < 0.05).
CONCLUSION—The IAP rise during isometric quadriceps contraction is a feature of all patients with an inflammatory based effusion irrespective of the duration of the effusion. This is not the case in patients with an ATE. In inflammatory synovitis the rise in intra-articular pressure with isometric quadriceps contraction relates to effusion volume. It is concluded that the inflammatory process prevents reflex muscle inhibition, a locally protective mechanism that minimises the potential for intermittent ischaemia/oxidative injury.

     

Increased transduction of human intestinal epithelial cells by adenoviral vectors in inflammatory bowel disease

BACKGROUND: Delivery of genes encoding anti-inflammatory proteins has been proposed as a strategy for the treatment of inflammatory bowel disease (IBD). The goal of this study was to assess the ability of a standard adenoviral vector to transfect epithelial cells in intestinal explants from patients with IBD compared with controls. METHODS: Endoscopic colon biopsies obtained from patients with no history of IBD and endoscopically normal colon (n = 4), patients with a history of ulcerative colitis (UC; n = 5), and patients with a history of Crohn's disease (CD; n = 3) were placed in explant culture and exposed to an adenoviral vector carrying the nuclear targeted beta-galactosidase reporter gene. RESULTS: X-Gal staining showed that the total number of transduced cells per square millimeter was greater in UC explants than in controls (mean, 11.3 versus 0.9 blue nuclei/mm, respectively; P < 0.02) and that the frequency of epithelial cell transduction was greater in UC explants than in controls (86% versus 47% of explants, respectively; P = 0.01). Transduction of mature columnar surface epithelial cells occurred exclusively in UC and CD explants and was not seen in controls. Attenuated epithelial cells at sites of tissue damage or ulceration showed increased transduction compared with mature columnar epithelial cells (62% versus 19% of occurrences, respectively; P < 0.0001). CONCLUSIONS: We conclude that intestinal epithelial cells from IBD patients are more readily transfected by standard adenoviral vectors than are those from control patients. These results suggest that targeting genes to inflamed intestine through the luminal route may be possible.     

Estrogen can protect splenocytes from the toxic effects of the environmental pollutant 4-tert-octylphenol

Four-tert-octylphenol (OP), an environmental pollutant, exerts apoptotic effects on cultured mouse splenocytes. Although OP binds to estrogen receptors, these apoptotic effects are not exerted by 17β-estradiol (E). It remained possible that OP might bind to estrogen receptors and subsequently exert apoptotic effects not exerted by E after it binds to the same receptors. It also remained possible that E-primed splenocytes might respond to OP differently than splenocytes not exposed to E. Thus, we investigated OP and E interactions on the viability of mouse splenocytes in culture. The total number of splenocytes (cells stained and not stained with trypan blue) was not altered or altered slightly after incubation with any agent for 24 h. Incubation of splenocytes in medium containing 5×10⁻⁵ or 5×10⁻⁷ M OP decreased the percentage of viable cells by approx 47% and 25%, respectively. The addition of 0.8×10⁻⁵ to 0.8×10⁻⁹ M E to cultures was without effect or decreased the percentage of viable cells by only approx 5%. The addition of these concentrations of E simultaneously with or at 2 h after the addition of 5×10⁻⁵ M or 5×10⁻⁷ M OP to cultures did not interfere with the OP-induced decreases in cell viability. By contrast, incubation of splenocytes in medium containing E for 2 h prior to the subsequent addition of either dose of OP blocked the OP-induced decreases in cell viability in a dose-response manner. There was a marked reduction in the percentage of viable cells (70%) when splenocytes were incubated with 0.5×10⁻⁵ M dexamethasone. The addition of 0.8×10⁻⁵ M E at 2 h prior to the addition of dexamethasone did not prevent the decreased cell viability. Incubation of cells in medium with 0.8×10⁻⁵ M testosterone caused a small decrease in splenocyte viability similar to that observed with E. However, unlike E, the addition of testosterone at 2 h prior to the addition of 5×10⁻⁵ M OP did not prevent the OP-induced decrease in cell viability. These data suggest the presence of estrogen receptors in some splenocytes. They also suggest that if OP binds to these estrogen receptors or other receptors in the absence or initial presence of E, the resulting effect is toxic to the cells. By contrast, exposure of splenocytes to E prior to their exposure to OP can prevent the toxicity of OP. A portion of this work has been published in abstract form in Molecular Biology of the Cell, Supplement to Vol. 7, 1996, Abstract 3843.